文章基本信息

标题：An In Vitro Whole-Organ Liver Engineering for Testing of Genetic Therapies
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作者：Maëlle Lorvellec ; Alessandro Filippo Pellegata ; Alice Maestri 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2020
卷号：23
期号：12
页码：1-31
DOI：10.1016/j.isci.2020.101808
语种：English
出版社：Elsevier
摘要：SummaryExplosion of gene therapy approaches for treating rare monogenic and common liver disorders created an urgent need for disease models able to replicate human liver cellular environment. Available models lack 3D liver structure or are unable to survive in long-term culture. We aimed to generate and test a 3D culture system that allows long-term maintenance of human liver cell characteristics.Thein vitrowhole-organ “Bioreactor grown Artificial Liver Model” (BALM) employs a custom-designed bioreactor for long-term 3D culture of human induced pluripotent stem cells-derived hepatocyte-like cells (hiHEPs) in a mouse decellularized liver scaffold. Adeno-associated viral (AAV) and lentiviral (LV) vectors were introduced by intravascular injection.Substantial AAV and LV transgene expression in the BALM-grown hiHEPs was detected. Measurement of secreted proteins in the media allowed non-invasive monitoring of the system.We demonstrated that humanized whole-organ BALM is a valuable tool to generate pre-clinical data for investigational medicinal products.Graphical AbstractDisplay OmittedHighlights•Generation of a perfused humanizedin vitrowhole liver bioreactor model: BALM•BALM improves maturation and long-term survival of human iPS-derived hepatocytes•BALM allows viral transduction of human iHEPs through its vasculature•BALM provides a tool for gene therapy testing of human iHEPsClinical Genetics; Bioengineering; Tissue Engineering